D3.3 Homeostasis
SL & HL+ AHL sectionsSL and HL, with AHL content · Organisms · Theme D
Big questions
- How does the body keep its internal conditions steady when the outside world keeps changing?
- What goes wrong, and why does it matter, when a control system fails?
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Homeostasis: a steady internal environment
The cells of a multicellular animal are bathed in tissue fluid, which is formed from blood plasma. This fluid is the cells’ immediate surroundings: their internal environment. Homeostasis is keeping the internal environment within narrow, preset limits, even when the external environment changes a lot.
Why it matters:
- Enzymes work best within a narrow range of temperature and pH; outside it, rates fall and proteins can denature.
- Water balance of cells depends on the solute concentration of the fluid around them: if it is too high, cells lose water by osmosis; if too low, they swell.
- A steady fuel supply (glucose) is needed by cells that respire constantly, especially brain cells.
Keeping conditions stable costs energy, but it lets animals stay active in very different and changing environments.
Variables controlled in humans
| Variable | Typical value | Main controller |
|---|---|---|
| Core body temperature | about 37 °C | hypothalamus (thermoregulation) |
| Blood pH | 7.35–7.45 | ventilation (C3.1 Integration of body systems) and the kidneys |
| Blood glucose concentration | about 4–8 mmol dm⁻³ through the day | pancreas (insulin and glucagon) |
| Blood osmotic concentration | about 0.3 osmol L⁻¹ | hypothalamus, ADH and kidneys (AHL) |
Each variable has a set point and limits either side of it. The body does not hold the value perfectly still: it fluctuates a little around the set point, and every deviation is corrected.
Negative feedback
Homeostasis depends on feedback control: information about the result of a process is used to adjust the process. Every homeostatic loop has three parts:
- Receptors detect the value of the variable (for example thermoreceptors, or the β cells’ own glucose sensing).
- A control centre (often in the brain, such as the hypothalamus) compares it with the set point.
- Effectors — muscles or glands — make a response.
Negative, not positive
In negative feedback, the response opposes the change. If the variable rises above the set point, the response brings it down; if it falls below, the response brings it up. The same loop therefore corrects deviations in both directions, and the variable stays within narrow limits.
In positive feedback, the response amplifies the change, pushing the variable further from where it started. This is useful when a process must be completed quickly, such as the rising oxytocin release during childbirth, but it cannot hold a variable steady. That is why homeostasis uses negative feedback.
Many variables have separate mechanisms that act in opposite directions, such as insulin and glucagon, or sweating and shivering. Having both gives finer and faster control than switching one mechanism on and off.
Hormonal control of blood glucose
Cells take glucose from the blood all the time, while glucose enters the blood in bursts after meals. Blood glucose concentration is held at about 5 mmol dm⁻³ by two hormones from the pancreas.
Scattered through the pancreas are small groups of endocrine cells, the islets of Langerhans. They contain:
- β (beta) cells, which secrete insulin;
- α (alpha) cells, which secrete glucagon.
These cells act as their own receptors: they detect the glucose concentration of the blood flowing past them and adjust their secretion. Both hormones are peptides, secreted by exocytosis into capillaries, carried dissolved in blood plasma to every part of the body and detected by receptors on the plasma membrane of target cells (C2.1 Chemical signalling).
When blood glucose is high (after a meal)
- β cells secrete more insulin; α cells secrete less glucagon.
- In muscle and fat cells, insulin causes more glucose transporter proteins to be inserted into the plasma membrane, so glucose uptake increases.
- Liver and muscle cells convert glucose to glycogen (glycogenesis); liver cells also make less new glucose and release less.
- Cells use more glucose in respiration, and fat cells convert glucose to fat.
- Blood glucose falls back towards the set point, so insulin secretion falls again.
When blood glucose is low (fasting, exercise)
- α cells secrete more glucagon; β cells secrete less insulin.
- Glucagon acts on liver cells, which break glycogen down to glucose (glycogenolysis) and release it into the blood. The liver also makes glucose from other molecules such as amino acids.
- Blood glucose rises back to the set point.
Blood glucose Insulin Glucagon
No diabetes. At 1 h 30 min, 30 minutes after a meal, blood glucose is 6.7 mmol dm⁻³ and rising; β cells are secreting more insulin, so liver and muscle cells take up glucose and store it as glycogen.
Show data table
| Time (h) | Glucose (mmol dm⁻³) | Insulin (relative) | Glucagon (relative) |
|---|---|---|---|
| 0 | 5.0 | 1.0 | 1.0 |
| 1 | 5.0 | 1.0 | 1.0 |
| 2 | 6.4 | 2.9 | 0.2 |
| 3 | 5.3 | 1.4 | 0.5 |
| 4 | 5.1 | 1.1 | 0.9 |
| 5 | 5.0 | 1.0 | 1.0 |
| 6 | 5.0 | 1.0 | 1.0 |
| 7 | 5.0 | 1.0 | 1.0 |
| 8 | 5.0 | 1.0 | 1.0 |
Qualitative model: the sizes of changes are realistic but simplified. Hormone levels are relative to a healthy person's fasting level (1). In real exercise, adrenaline also stimulates glycogen breakdown.
Text description of this simulation
A simulation of blood glucose concentration over eight hours. You choose a person (no diabetes, type 1 diabetes or type 2 diabetes), move a time slider and add meals or 45-minute periods of exercise at that time. A graph shows blood glucose with the typical range shaded and the renal threshold marked, and a second graph shows insulin and glucagon. A panel shows the islet cells of the pancreas, the blood glucose concentration, whether the liver and muscles are storing glucose as glycogen or breaking glycogen down, and whether glucose is appearing in the urine. In a person without diabetes a meal raises glucose, β cells secrete more insulin and glucose returns to about 5 mmol dm⁻³; exercise lowers glucose, glucagon rises and glucose recovers. With type 1 diabetes no insulin is made and glucose stays very high unless insulin is injected. With type 2 diabetes insulin is high but cells respond weakly, so glucose is raised. The model is qualitative.
Type 1 and type 2 diabetes
Diabetes mellitus is a condition in which blood glucose is often too high because insulin is lacking or does not work properly. When blood glucose rises above about 10 mmol dm⁻³ (the renal threshold), the kidneys cannot reabsorb it all and glucose appears in the urine. Persistently high glucose damages blood vessels, nerves, kidneys and the retina over many years.
| Type 1 | Type 2 | |
|---|---|---|
| Physiological change | the immune system destroys β cells (autoimmune), so little or no insulin is made | target cells become insulin resistant: they respond weakly to insulin, so less glucose is taken up; β cells may later fail too |
| Insulin in blood | very low or absent | normal or high at first |
| Typical onset | usually childhood or early adulthood; can be sudden | usually later adulthood, gradual, often unnoticed for years; increasingly seen in younger people |
| Risk factors | family history (genetic susceptibility); possibly environmental triggers such as viral infections | obesity (especially around the abdomen), physical inactivity, diet high in sugar and fat and low in fibre, increasing age, family history and ethnicity |
| Prevention | not currently preventable | keep a healthy body mass, exercise regularly, eat a diet low in refined sugar and high in fibre |
| Treatment | regular blood glucose testing and insulin by injection or pump, matched to meals | diet, exercise and weight loss; drugs that improve insulin sensitivity or glucose handling; insulin if needed later |
About nine in ten people with diabetes have type 2. Insulin cannot be taken by mouth because it is a protein: it would be digested.
Thermoregulation by negative feedback
Thermoregulation keeps core body temperature close to its set point of about 37 °C. It is a negative feedback loop:
- Receptors. Peripheral thermoreceptors are nerve endings in the skin that detect skin temperature; because skin cools first, they give early warning of heat loss. Central thermoreceptors in the hypothalamus and elsewhere in the body core monitor the temperature of the blood.
- Control centre. The hypothalamus integrates this information, compares it with the set point and sends out signals.
- Effectors. Nerves carry signals to skin arterioles, sweat glands, the erector muscles of hairs, skeletal muscle and brown adipose tissue. The hypothalamus also controls hormone secretion by the pituitary gland.
Thyroxine
When the body is cold, the hypothalamus secretes a releasing hormone (TRH) that causes the anterior pituitary gland to secrete TSH, which stimulates the thyroid gland to secrete thyroxine (the IB guide spells it thyroxin). Thyroxine increases the metabolic rate of most body cells, especially active tissues such as liver and muscle, so more heat is released by respiration. When the body is too warm, thyroxine secretion falls. This hormonal route is slower than the nervous responses but has longer-lasting effects.
Muscle and adipose tissue as effectors
- Skeletal muscle generates heat when it contracts. In shivering, rapid involuntary contractions release heat without producing movement.
- Brown adipose tissue generates heat by uncoupled respiration (see below).
- White adipose tissue under the skin is a passive insulator rather than an effector.
Control pathway
Effectors in the skin and below
- Core temperature
- 37.0 °C
- Skin blood flow
- 40% of maximum
- Sweat rate
- 0.0 dm³ h⁻¹
- Shivering
- none
- Brown fat heat
- none
- Thyroxine
- normal
At 24 °C and at rest the body is in heat balance: core temperature is 37.0 °C and only small changes in skin blood flow are needed.
Qualitative model of a lightly clothed adult; values are simplified. The thyroxine response takes hours to days, much slower than the nervous responses. Behavioural responses (clothing, shade, activity) are not included.
Text description of this simulation
A simulation of temperature control in a lightly clothed adult. Sliders set the air temperature from −10 to 45 °C and the level of activity. The left panel shows the control pathway: peripheral thermoreceptors in the skin and central thermoreceptors send signals to the hypothalamus, which controls effectors through nerves and, through the pituitary gland and thyroid, the secretion of thyroxine. The right panel is a section through skin and the tissues below. In the cold, skin arterioles constrict, a shunt vessel opens, the hairs are raised by erector muscles, skeletal muscle shivers, brown adipose tissue releases heat and thyroxine rises. In heat or during exercise, arterioles dilate, more blood flows through the skin capillaries and sweat glands secrete sweat. Core temperature stays close to 37 °C; a checkbox switches the responses off to show that core temperature would then drift into hypothermia or hyperthermia. The model is qualitative.
Temperature control mechanisms in humans
Birds and mammals are endotherms: they keep their core temperature constant using both physiological responses (inside the body) and behavioural responses (seeking shade or sun, huddling, changing posture or activity; in humans, also clothing). Only the human physiological details are needed.
| Response | When | How it works |
|---|---|---|
| Vasodilation | too hot | circular smooth muscle in the walls of arterioles supplying the skin relaxes, widening them; more blood flows through skin capillaries, the skin warms and loses more heat |
| Sweating | too hot | sweat glands secrete sweat onto the skin; evaporation of its water absorbs a lot of heat (high latent heat of vaporization), cooling the skin and the blood flowing through it |
| Vasoconstriction | too cold | arterioles supplying the skin constrict and shunt vessels divert blood away from skin capillaries; the skin cools and less heat is lost |
| Shivering | too cold | rapid involuntary contractions of skeletal muscle release heat |
| Uncoupled respiration | too cold | brown adipose tissue, rich in mitochondria, oxidizes fat; protons leak back across the inner mitochondrial membrane instead of driving ATP synthase, so energy is released as heat rather than as ATP |
| Hair erection | too cold | erector muscles pull hairs upright, trapping a thicker layer of insulating air; in furry mammals this is effective, but humans have little body hair, so it only gives “goosebumps” |
Brown adipose tissue is most abundant in newborn babies (and in hibernating mammals), but adults keep some, for example in the neck and around the upper chest.
The kidney: osmoregulation and excretion
The kidneys have two separate roles:
- Excretion is the removal of the toxic waste products of metabolism from the body. The main example is urea, made in the liver when excess amino acids are broken down. Kidneys also remove other unwanted solutes such as drugs and some food pigments.
- Osmoregulation is control of the osmotic concentration of the blood and tissue fluid — the total concentration of dissolved particles that affect osmosis. It is measured in osmoles per litre (osmol L⁻¹); human blood plasma is about 0.3 osmol L⁻¹. The kidneys osmoregulate by varying the amounts of water and salts lost in urine.
Egestion of faeces is not excretion: most of faeces never crossed a cell membrane into the body.
Each kidney has an outer cortex, an inner medulla made of renal pyramids, and a renal pelvis that drains into the ureter. Blood arrives in the renal artery and leaves in the renal vein. The work is done by about a million microscopic tubules in each kidney, the nephrons. Each nephron starts in the cortex, dips into the medulla in a loop and drains into a collecting duct that carries urine to the pelvis.
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Text description of this visual
The first model is one nephron with its blood vessels, drawn schematically. The pale upper band is the cortex and the grey lower band is the medulla, which gets darker with depth to show that the solute concentration of its tissue fluid rises towards the inner medulla. In the cortex, a wide afferent arteriole carries blood into the glomerulus, a knot of capillaries inside the cup-shaped Bowman's capsule, and a narrower efferent arteriole carries it out to peritubular capillaries wound round the tubules. From the capsule the proximal convoluted tubule coils through the cortex, then the thin descending limb of the loop of Henle runs straight down into the medulla, turns in a hairpin and returns as the wider ascending limb. The distal convoluted tubule coils back past its own renal corpuscle and joins a collecting duct, which is shared with other nephrons and runs down through the medulla towards the renal pelvis. The vasa recta, a hairpin of capillaries, lie beside the loop. Enlarged insets show the filtration barrier (fenestrated capillary wall, basement membrane and podocytes) and a cross-section of the proximal convoluted tubule wall with microvilli and mitochondria. Seven steps follow blood and filtrate through the nephron. The second model is a kidney cut in half from top to bottom, showing the outer cortex, the renal pyramids of the medulla, the renal pelvis and ureter, and the renal artery and vein at the hilum.
Nephron
- Cortex
- The outer region of the kidney. It contains the renal corpuscles (glomerulus and Bowman's capsule) and the proximal and distal convoluted tubules.
- Medulla
- The inner region, containing the loops of Henle and collecting ducts. The solute concentration of its tissue fluid rises with depth (shown by darker shading), up to about 1.2 osmol L⁻¹ in humans.
- Afferent arteriole
- Brings blood to the glomerulus. It is wider than the efferent arteriole, so blood enters faster than it can leave and the pressure inside the glomerular capillaries is high.
- Efferent arteriole
- Carries blood away from the glomerulus. Being narrower than the afferent arteriole, it keeps glomerular pressure high. It leads to a second capillary network, the peritubular capillaries.
- Glomerulus
- A ball of capillaries with a long, contorted route and very leaky (fenestrated) walls. The high pressure forces about a fifth of the plasma out into Bowman's capsule — ultrafiltration.
- Bowman's capsule
- A double-walled cup round the glomerulus. Its inner wall is made of podocytes; the space between the walls collects the glomerular filtrate and leads into the proximal convoluted tubule.
- Fenestrated capillary wall (enlarged)
- The endothelial cells of glomerular capillaries have many wide pores (fenestrations, up to about 100 nm across). They let plasma through freely but hold back blood cells.
- Basement membrane (the filter)
- A continuous non-cellular mesh of glycoproteins round the capillaries. It is the actual filter — small solutes and water pass, but most plasma proteins are held back by their size and negative charge.
- Podocytes (enlarged)
- Cells of the inner wall of Bowman's capsule. Their foot processes wrap round the capillaries, leaving narrow filtration slits that also help stop proteins leaving the blood.
- Proximal convoluted tubule
- The longest part of the nephron, coiled in the cortex. It reabsorbs all the glucose and amino acids and most of the water, Na⁺ and other ions from the filtrate, returning them to the blood.
- PCT wall in section (enlarged)
- A single layer of cells with microvilli facing the lumen (a large surface area for reabsorption) and many mitochondria near the base, supplying ATP for the active transport of Na⁺.
- Descending limb of the loop of Henle
- Permeable to water but not to Na⁺. As it passes down into ever more concentrated medulla, water leaves the filtrate by osmosis.
- Ascending limb of the loop of Henle
- Impermeable to water. Na⁺ is actively transported out of the filtrate (Cl⁻ follows), raising the solute concentration of the medulla; the filtrate becomes more dilute as it rises.
- Distal convoluted tubule
- Coils back through the cortex, passing its own glomerulus. Ions such as Na⁺, K⁺ and H⁺ are exchanged here to fine-tune the blood's ion balance and pH.
- Collecting duct
- Receives filtrate from several nephrons and carries it through the medulla to the renal pelvis. ADH makes its walls permeable to water (aquaporins), so water is reabsorbed by osmosis.
- Peritubular capillaries
- A capillary network fed by the efferent arteriole and wrapped round the convoluted tubules. It takes up the reabsorbed water and solutes and returns them to the circulation.
- Vasa recta
- Long hairpin capillaries running beside the loops of Henle in the medulla. They carry away reabsorbed water without washing away the high solute concentration of the medulla.
- Blood enters the glomerulus. Blood arrives in the cortex through the afferent arteriole, which is wider than the efferent arteriole leaving the glomerulus. Blood flows in faster than it can leave, and its route through the coiled capillaries is long, so the blood pressure in the glomerulus is unusually high.
- Ultrafiltration into Bowman's capsule. The high pressure forces plasma out through the fenestrated capillary wall, the basement membrane and the slits between podocyte foot processes. Water, glucose, amino acids, ions and urea pass; blood cells and most plasma proteins stay in the blood. The fluid collected by Bowman's capsule is glomerular filtrate.
- Selective reabsorption in the PCT. As filtrate flows along the proximal convoluted tubule, Na⁺ is pumped out of the wall cells, glucose and amino acids are reabsorbed by cotransport with Na⁺, and water follows by osmosis. All the glucose and amino acids and most of the water and ions return to the blood in the peritubular capillaries; urea and other wastes stay in the filtrate.
- The loop of Henle concentrates the medulla. In the ascending limb, which is impermeable to water, Na⁺ is actively transported out into the medulla (Cl⁻ follows). This keeps the solute concentration of the medulla high. Water leaves the descending limb by osmosis into this concentrated tissue fluid and is carried away by the vasa recta.
- Distal convoluted tubule. The filtrate leaving the ascending limb is dilute. In the distal convoluted tubule, back in the cortex, ion concentrations are adjusted further before the filtrate drains into a collecting duct shared with other nephrons.
- Water reabsorption in the collecting duct. The collecting duct runs down through the increasingly concentrated medulla. When ADH is present, aquaporins are inserted into its wall cells and water leaves the filtrate by osmosis, so a small volume of concentrated urine flows on to the renal pelvis. With little ADH, most of this water stays in the duct.
- Reabsorbed substances return to the blood. Blood from the efferent arteriole flows through the peritubular capillaries round the convoluted tubules and the vasa recta in the medulla, collecting the reabsorbed water and solutes, and then drains into venules and on to the renal vein.
Whole kidney
- Cortex
- The outer layer, under a tough fibrous capsule. It contains all the glomeruli, Bowman's capsules and convoluted tubules, and dips between the pyramids as renal columns.
- Medulla (renal pyramid)
- The medulla is made of cone-shaped pyramids. Their stripes are loops of Henle and collecting ducts running towards the tip (papilla), where urine drains out.
- Renal pelvis
- A funnel-shaped cavity that collects urine from the collecting ducts through cup-like calyces round the tips of the pyramids, and leads into the ureter.
- Ureter
- A muscular tube that carries urine from the renal pelvis down to the bladder.
- Renal artery
- A branch of the aorta bringing oxygenated blood, with its wastes, to the kidney. Inside it branches between the pyramids and finally into the afferent arterioles of about a million nephrons.
- Renal vein
- Carries filtered blood, with a lower concentration of urea, from the kidney to the inferior vena cava. At the hilum it lies in front of the artery.
- A nephron (not to scale)
- The functional unit of the kidney. Its renal corpuscle and convoluted tubules are in the cortex; its loop of Henle dips into a pyramid and its collecting duct opens at the papilla.
Ultrafiltration and reabsorption: glomerulus, Bowman's capsule and PCT
Ultrafiltration
Each nephron begins with a glomerulus, a knot of capillaries, enclosed in a cup-shaped Bowman’s capsule. Blood pressure in the glomerulus is much higher than in other capillaries because:
- the afferent arteriole that brings blood in is wider than the efferent arteriole that takes it away;
- the route through the coiled capillaries is long and contorted.
The pressure forces plasma out through three layers:
- the fenestrated capillary wall: endothelial cells with many wide pores (up to about 100 nm), which hold back blood cells;
- the basement membrane, a mesh of negatively charged glycoproteins that acts as the filter, holding back most plasma proteins by size and charge;
- podocytes, cells of the inner wall of the capsule, whose foot processes wrap round the capillaries with narrow filtration slits between them.
The glomerular filtrate contains water, glucose, amino acids, ions, urea and other small solutes at almost the same concentrations as in plasma, but almost no protein. Around 180 dm³ is produced per day, yet only about 1.5 dm³ of urine is excreted: most of the filtrate must be reabsorbed.
Selective reabsorption in the proximal convoluted tubule
The proximal convoluted tubule (PCT) is long and coiled, giving the filtrate time and surface to be processed. Its wall is one layer of cells with microvilli facing the filtrate and many mitochondria near the base.
- Na⁺ is pumped out of the wall cells into the tissue fluid by Na⁺/K⁺ pumps using ATP; Na⁺ then diffuses into the cells from the filtrate. Cl⁻ follows by attraction to the positive charge.
- Glucose and amino acids are taken up by cotransport with Na⁺ (indirect active transport, B2.1 Membranes and membrane transport). Normally all of them are reabsorbed.
- Water follows by osmosis, because solute reabsorption lowers the solute concentration of the filtrate.
By the end of the PCT, all glucose and amino acids and around two-thirds or more of the water and Na⁺ have returned to the blood in the peritubular capillaries. Urea and other wastes are not reabsorbed (or only partly), so they become more concentrated in the filtrate.
The loop of Henle
After the PCT, the filtrate flows down the descending limb of the loop of Henle into the medulla, turns in a hairpin and flows back up the ascending limb to the cortex.
The ascending limb is impermeable to water, but it actively transports Na⁺ out of the filtrate into the tissue fluid of the medulla (Cl⁻ follows). Because water cannot follow, this does two things:
- the solute concentration of the medulla stays high, rising from about 0.3 osmol L⁻¹ at the boundary with the cortex to about 1.2 osmol L⁻¹ deep in the medulla in humans;
- the filtrate leaving the ascending limb is dilute.
The descending limb is permeable to water, so water leaves it by osmosis into the concentrated medulla and is carried away by the vasa recta. Because the two limbs carry filtrate in opposite directions side by side, the small concentration difference created at each level is multiplied along the loop. Longer loops can build a more concentrated medulla.
The point of all this is what happens next: the collecting ducts pass through this hypertonic medulla, so water can be drawn out of them by osmosis.
Osmoregulation: ADH and the collecting duct
The water reabsorbed in the collecting ducts is adjusted to keep blood osmotic concentration at its set point — another negative feedback loop.
- Receptors: osmoreceptors in the hypothalamus detect the solute concentration of the blood. When it is high, they lose water by osmosis and shrink.
- Hormone: antidiuretic hormone (ADH) is made by neurosecretory cells in the hypothalamus and released from the posterior pituitary gland into the blood.
- Target: cells of the collecting duct walls. ADH binds to receptors on them, and vesicles containing aquaporins fuse with the membrane facing the filtrate, so the duct becomes permeable to water. When ADH falls, aquaporins are removed from the membrane by endocytosis and stored in vesicles again.
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Text description of this animation
A diagram in three parts: the hypothalamus with an osmoreceptor and the posterior pituitary gland (top left); a gauge of blood solute concentration with its set point (top right); and a collecting duct cell with the filtrate in the duct on its left and the concentrated tissue fluid of the medulla on its right. A blood vessel links the pituitary to the kidney. Six steps show negative feedback when blood becomes too concentrated (more ADH, aquaporins inserted, more water reabsorbed, concentrated urine) and when it becomes too dilute (less ADH, aquaporins removed, dilute urine).
- Blood becomes too concentrated. After sweating or not drinking, the solute concentration of the blood rises above its set point. Osmoreceptors in the hypothalamus lose water by osmosis and shrink, and they detect this change.
- More ADH is secreted. Signals from the hypothalamus cause the posterior pituitary gland to secrete more antidiuretic hormone (ADH) into the blood, which carries it to the kidneys.
- Aquaporins are inserted. ADH binds to receptors on collecting duct cells. Vesicles containing aquaporins move to the membrane facing the filtrate and fuse with it, so the duct wall becomes much more permeable to water.
- More water is reabsorbed. Water moves by osmosis from the filtrate, through the aquaporins, into the concentrated tissue fluid of the medulla and then into the blood. A small volume of concentrated urine is produced and the blood solute concentration falls back to the set point — negative feedback.
- Blood becomes too dilute. After drinking a lot of water, blood solute concentration falls below the set point. Osmoreceptors gain water and swell, and the pituitary gland secretes less ADH, so the ADH in the blood falls.
- Aquaporins are removed. With less ADH, aquaporins are taken back into the cell by endocytosis and stored in vesicles. The duct wall becomes less permeable, little water is reabsorbed, a large volume of dilute urine is produced and blood solute concentration rises back to the set point.
| Blood osmotic concentration | too high (dehydrated) | too low (excess water) |
|---|---|---|
| ADH secreted by the pituitary | more | less |
| Aquaporins in collecting duct membranes | more (vesicles fuse with membrane) | fewer (taken into vesicles) |
| Water reabsorbed | more | less |
| Urine | small volume, concentrated (hypertonic) | large volume, dilute (hypotonic) |
| Effect on blood | concentration falls to set point | concentration rises to set point |
Blood supply to organs changes with activity
The heart cannot supply every organ at its maximum rate at the same time, so blood is redirected according to need. Circular smooth muscle in arteriole walls relaxes (vasodilation) to increase flow to an organ, or contracts (vasoconstriction) to reduce it. Sympathetic nerves, hormones such as adrenaline and local signals from active tissue (low O₂, high CO₂) control these changes. Cardiac output itself also changes (B3.2 Transport).
- Vigorous exercise. Cardiac output rises about threefold (more in trained athletes). Arterioles in skeletal muscle dilate and flow to muscle rises over tenfold, supplying O₂ and glucose and removing CO₂ and heat. Flow to the gut and kidneys falls through vasoconstriction, as digestion and urine production can be reduced for a while. Brain flow is kept roughly constant (it may rise slightly).
- Wakeful rest. The kidneys and gut together receive over two-fifths of the cardiac output; flow to the gut is higher after a meal. Muscles receive enough for posture and tone.
- Sleep. Cardiac output is lower. Muscles are relaxed and receive less blood; kidney flow falls a little, so less urine is produced at night. Brain flow is maintained overall, though it varies between sleep stages.
Interpreting the data
Percentages of cardiac output show the redistribution clearly:
| Organ | At rest | Vigorous exercise |
|---|---|---|
| Skeletal muscle | 1000 / 5800 ≈ 17% | 12 500 / 17 500 ≈ 71% |
| Gut | ≈ 23% | ≈ 3% |
| Brain | ≈ 13% | ≈ 5% |
| Kidneys | ≈ 19% | ≈ 3% |
The brain’s share falls during exercise even though its actual flow does not: always say whether you are comparing absolute flow (cm³ min⁻¹) or percentage of cardiac output.
Must-know definitions
- Homeostasis
- Keeping the internal environment of an organism (the tissue fluid and blood around its cells) within narrow limits, despite changes in the external environment. Human examples: body temperature, blood glucose, blood pH and the osmotic concentration of blood.
- Negative feedback
- A control system in which a change in a variable away from its set point triggers responses that reverse the change, returning the variable towards the set point whether it had risen above or fallen below it.
- Insulin
- A peptide hormone secreted by β cells in the islets of the pancreas when blood glucose rises. It travels in blood plasma and makes liver, muscle and fat cells take up glucose; liver and muscle store it as glycogen (glycogenesis). Blood glucose falls.
- Glucagon
- A peptide hormone secreted by α cells in the islets of the pancreas when blood glucose falls. It makes liver cells break glycogen down to glucose (glycogenolysis) and release it into the blood. Blood glucose rises.
- Type 1 diabetes
- The immune system destroys the β cells, so little or no insulin is secreted. Usually begins in childhood or early adulthood; treated by monitoring blood glucose and giving insulin by injection or pump.
- Type 2 diabetes
- Target cells become less sensitive to insulin (insulin resistance), so glucose uptake is reduced even though insulin is secreted. Risk is raised by obesity, inactivity, poor diet, age and family history; managed by diet, exercise, weight loss and drugs.
- Thermoregulation
- Negative feedback control of core body temperature (about 37 °C in humans). Peripheral and central thermoreceptors signal to the hypothalamus, which controls effectors by nerves and, through the pituitary gland, thyroxine secretion.
- Uncoupled respiration
- In brown adipose tissue, mitochondria oxidize fat but a protein in the inner membrane lets protons leak back without passing through ATP synthase, so the energy is released as heat instead of being used to make ATP.
- OsmoregulationAHL
- Control of the osmotic concentration of body fluids (the total concentration of dissolved solutes that affect osmosis, measured in osmol L−1) by varying how much water and salt is lost in urine.
- UltrafiltrationAHL
- Filtration of blood plasma under high pressure in the glomerulus. Water and small solutes pass through the fenestrated capillary wall, the basement membrane (the filter) and the filtration slits between podocytes; blood cells and most proteins are held back.
- ADH and aquaporinsAHL
- Antidiuretic hormone, secreted by the posterior pituitary when osmoreceptors in the hypothalamus detect a high blood solute concentration. It causes vesicles carrying aquaporins to fuse with the membranes of collecting duct cells, so more water is reabsorbed.
Common exam mistakes
Loses marks Negative feedback means the response is negative, or reduces the variable.
Write instead Negative feedback means the response opposes the change: if the variable rises it is brought down, and if it falls it is brought up, returning it towards the set point.
Loses marks Insulin converts glucose into glycogen.
Write instead Insulin is a signal, not an enzyme. It binds to receptors on target cells, which then take up more glucose and activate their own enzymes to make glycogen.
Loses marks Glucagon makes muscle cells break down glycogen and release glucose into the blood.
Write instead Glucagon acts mainly on liver cells. Muscle glycogen is broken down only for the muscle's own use; muscle cells do not release glucose into the blood.
Loses marks Confusing glucagon (the hormone) with glycogen (the storage polysaccharide).
Write instead Glucagon is a peptide hormone from α cells; glycogen is the branched polymer of glucose stored in liver and muscle. Glucagon causes glycogen to be broken down.
Loses marks Type 2 diabetes is caused by a lack of insulin, like type 1.
Write instead In type 2, insulin is usually still secreted (often more than normal at first), but target cells respond weakly to it — insulin resistance. In type 1, the β cells are destroyed and insulin is not made.
Loses marks In heat, capillaries move closer to the skin surface (vasodilation of capillaries).
Write instead Capillaries do not move and have no muscle in their walls. The arterioles supplying the skin dilate, so more blood flows through the skin capillaries and more heat is lost.
Loses marks Sweat cools the body because it is cold, or simply because it is wet.
Write instead Cooling happens when water in sweat evaporates: breaking hydrogen bonds takes a lot of heat energy (high latent heat of vaporization) from the skin.
Loses marks The glomerulus filters out proteins and glucose is not filtered.
Write instead Glucose, amino acids, ions, urea and water are all filtered; it is mainly proteins and cells that are held back. Glucose is absent from normal urine because all of it is reabsorbed in the proximal convoluted tubule.
AHLLoses marks ADH makes the collecting duct actively pump water out of the filtrate.
Write instead Water is never actively pumped. ADH increases the number of aquaporins in the membranes of collecting duct cells, and water moves passively by osmosis into the concentrated tissue fluid of the medulla.
AHLLoses marks The descending limb of the loop of Henle pumps out sodium ions.
Write instead Na⁺ is actively transported out of the ascending limb, which is impermeable to water. The descending limb is permeable to water, which leaves it by osmosis.
AHL
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Define homeostasis and name four variables it controls in humans.
Keeping the internal environment within narrow, preset limits despite changes outside. Examples are body temperature, blood glucose, blood pH and the osmotic concentration of blood.
Why does homeostasis use negative rather than positive feedback?
Negative feedback reverses a deviation above or below the set point, so the variable stays stable. Positive feedback amplifies a deviation, moving the variable further from the set point.
Name the three parts of a homeostatic control loop.
Receptors detect the variable; a control centre compares it with the set point; effectors (muscles or glands) respond to reverse the change.
Which cells secrete insulin and glucagon, and where are they?
β cells secrete insulin and α cells secrete glucagon. Both are in the islets of Langerhans, small groups of endocrine cells scattered through the pancreas.
Effects of insulin on target cells
Muscle and fat cells take up more glucose (more glucose transporters in the membrane); liver and muscle cells convert glucose to glycogen; cells respire more glucose; liver releases less glucose. Blood glucose falls.
Effects of glucagon on target cells
Liver cells break glycogen down to glucose (glycogenolysis), make glucose from other molecules and release it into the blood. Blood glucose rises.
Type 1 vs type 2 diabetes — the physiological change
Type 1 — autoimmune destruction of β cells, so little or no insulin is made. Type 2 — target cells are insulin resistant, so they take up little glucose even though insulin is secreted.
Risk factors and treatment of type 2 diabetes
Risk factors — obesity, physical inactivity, diet high in sugar and fat and low in fibre, age, family history. Prevention and treatment — healthy weight, exercise, diet; drugs, and insulin if needed.
Role of thyroxine in thermoregulation
In the cold the hypothalamus causes the pituitary gland to secrete TSH, so the thyroid secretes more thyroxine. Thyroxine raises the metabolic rate of body cells, releasing more heat. It is a slower response than the nervous ones.
Human responses to overheating
Vasodilation of arterioles supplying the skin (more blood flows near the surface and loses heat) and sweating (evaporation of water from sweat absorbs heat). Thyroxine secretion falls.
Human responses to cold
Vasoconstriction of skin arterioles, shivering (skeletal muscle), uncoupled respiration in brown adipose tissue, hair erection, and more thyroxine.
Excretion vs osmoregulation
Excretion — removing toxic waste products of metabolism, such as urea. Osmoregulation — controlling the osmotic concentration (osmol L⁻¹) of body fluids by varying the water and salt lost in urine.
Three layers of the ultrafiltration barrier
Fenestrated capillary endothelium (holds back cells), basement membrane (the filter; holds back most proteins) and podocytes with filtration slits between their foot processes.
What is reabsorbed in the proximal convoluted tubule, and how?
All glucose and amino acids (cotransport with Na⁺), most Na⁺ (active transport) and Cl⁻, and most water (osmosis). Microvilli give a large surface area; mitochondria supply ATP.
Role of the loop of Henle
The ascending limb, impermeable to water, actively transports Na⁺ out into the medulla, keeping its osmotic concentration high. This lets water be reabsorbed from the collecting ducts by osmosis.
How does ADH change the collecting duct?
ADH from the posterior pituitary causes vesicles containing aquaporins to fuse with the collecting duct cells' membranes, so more water is reabsorbed by osmosis. Less ADH — aquaporins are taken back into vesicles.
Blood flow changes during vigorous exercise
Skeletal muscle flow rises over tenfold (vasodilation); gut and kidney flow fall (vasoconstriction); brain flow stays about the same, so its share of cardiac output falls.
Last reviewed 19 October 2026. Spotted a mistake? Report it.